DESCRIPTION: Experiments outlined in this proposal are intended to examine the biochemical and molecular mechanisms of motor neuron death during development. The proposed research will focus on elucidating some of the intracellular events that mediate neuronal death as well as how the dying neuron may signal non-neuronal cells to respond to its death. The work will provide the foundation for the research focus of the principal investigators new laboratory. The three specific aims are to: (1) isolate and characterize novel neuronal death genes; (2) to isolate and characterize ICE-like genes that mediate motor neuron death and, (3) to isolate and characterize biochemical and molecular changes within dying motor neurons that may signal phagocytic removal of their debris. It can be expected that understanding the intra- and intercellular processes that regulate neuron death will contribute to our understanding of basic CNS developmental processes as well as provide insights into the cell death that occurs following injury or in neurodegenerative diseases.